Motility Disorders include those diseases characterized by an abnormality of the autonomic nervous system. These include diseases of idiopathic or known causes such as Functional Bowel Diseases and autonomic neuropathies of diabetes, scleroderma, and Parkinson's Disease.
Treatment of the diseases of the autonomic nervous system has been limited to a few drugs approved by the Federal Drug Administration. The most common drug therapy has been with metoclopromide, a dopamine antagonist or with acetylcholine agonists such as bethanecol. Such therapy has had limited success in patients with mild to moderate disease symptoms. New experimental drugs tested for the treatment of patients with disease of the Autonomic Nervous System include the drugs domperidone (dopamine antagonist which does not cross the blood-brain barrier) and cisapride which enhances release of acetylcholine. While these experimental drugs provide limited relief of mild to moderate symptoms, they have not been effective for patients with severe symptoms.
Chronic, unexplained abdominal pain, nausea, vomiting and altered bowel habits are common symptoms of the intractable bowel disorders presently called "Functional Bowel Disease" or "Irritable" Bowel Syndrome. The cause and pathophysiology remain unknown, but evidence suggests that the disease may be related to abnormalities of intestinal smooth muscle or the enteric nervous system, or both, and is a systemic problem (Mathias and Finelli, Contemporary Issues in Gastroenterology, S. Cohen and R. D. Soloway (eds) Vol. 639-59, 1987).
A recent survey by Mitchell and Drossman (Gastroenterology 92:1283-1284, 1987) found that 47% of patients seen by gastroenterologists had functional complaints; i.e., gastrointestinal symptoms in the absence of objective findings. A similar survey of certified specialists in internal medicine indicated that 13% of their patients had chronic pain without objective findings (Margolis et al., Pain 20:151-156, 1984).
In these functional diseases, women are more commonly affected than men, with the ratio approximately 20:1 (women:men) (Mathias and Finelli, 1987). Often these patients are considered psychoneurotic (Woodhouse and Bockner, Br. J. Surgery 66:348-349, 1979; Drossman Am. J. Psychiatry 139: 1549-1557, 1982) and told they must live with their problems. Psychotherapy, in general, has not added much to improve the general condition of those with moderate-to-severe functional disease.
Recognized syndromes of Functional Bowel Disease include Gastroduodenal Motor Dysfunction, Intestinal Pseudo-obstruction both idiopathic and of known cause, Idiopathic Intestinal Hollow Visceral Myopathy/Neuropathy, Severe Intestinal Constipation and Post-Vagotomy Syndromes such as the Roux-en-Y Syndrome. Previously, these diseases were thought to be disorders without an organic basis, however, recent evidence now suggests these diseases involve alterations of both the muscle of the intestinal wall and the nerves of the myenteric plexus (Mathias and Finelli, Contemporary Issues in Gastroenterology, Vol. 6, Cohen and Soloway, eds., New York, Churchill Livingstone, 1987, pages 39-58). Recent evidence has also shown abnormal gastrointestinal motility in many patients (You et. al., Annals Internal Medicine 95:449-451, 1981; Rees et. al., Gastroenterology 78:360-365, 1980; and Mathias and Finelli, 1987). Treatment of such patients has been by medications such as opiates, to enhance gastrointestinal motor activity, or antiemetic effect (McCallum, American Journal Gastroenterology 88:1008-1016, 1985). Because of their effects on the upper GI tract, dopamine antagonists such as metoclopramide and domperidone have been tested for therapeutic effects. Results of such therapy have varied, depending upon the antagonist, dosage, treatment regimen, and patient population, but in general such therapy appears to lessen the symptoms of disease.
It would be of great utility to provide a novel treatment of Functional Bowel Disease or Motility Disorders which would alleviate the debilitating symptoms which characterize the disease.